| RRC ID |
34922
|
| Author |
Kawashima-Goto S, Imamura T, Tomoyasu C, Yano M, Yoshida H, Fujiki A, Tamura S, Osone S, Ishida H, Morimoto A, Kuroda H, Hosoi H.
|
| Title |
BCL2 Inhibitor (ABT-737): A Restorer of Prednisolone Sensitivity in Early T-Cell Precursor-Acute Lymphoblastic Leukemia with High MEF2C Expression?
|
| Journal |
PLoS One
|
| Abstract |
Early T-cell precursor-acute lymphoblastic leukemia (ETP-ALL) has been identified as a high-risk subtype of pediatric T-cell acute lymphoblastic leukemia (T-ALL). Conventional chemotherapy is not fully effective for this subtype of leukemia; therefore, potential therapeutic targets need to be explored. Analysis of the gene expression patterns of the transcription factors in pediatric T-ALL revealed that MEF2C and FLT3 were expressed at higher levels in ETP-ALL than typical T-ALL. Using human T-ALL and BaF3 cell lines with high expression levels of MEF2C, the present study tested whether the BCL2 inhibitor (ABT-737) restores the sensitivity to prednisolone (PSL), because MEF2C causes PSL resistance, possibly by augmenting the anti-apoptotic activity of BCL2. Treatment with PSL and ABT-737 caused a significant reduction in the IC50 of PSL in the MEF2C-expressing LOUCY cells, in addition to the MEF2C-transduced BaF3 cells, but not in the non-MEF2C-expressing Jurkat cells. The combination treatment significantly accelerated the killing of primary leukemic blast cells of ETP-ALL with high expression levels of MEF2C, which were co-cultured with murine stromal cells. These findings suggest that BCL2 inhibitors may be a therapeutic candidate in vivo for patients with ETP-ALL with high expression levels of MEF2C.
|
| Volume |
10(7)
|
| Pages |
e0132926
|
| Published |
2015-1-1
|
| DOI |
10.1371/journal.pone.0132926
|
| PII |
PONE-D-15-04635
|
| PMID |
26172269
|
| PMC |
PMC4501565
|
| MeSH |
Animals
Apoptosis / drug effects
Apoptosis / genetics
Biphenyl Compounds / pharmacology*
Cell Line, Tumor
Coculture Techniques
Gene Expression Regulation, Leukemic / drug effects
Gene Expression Regulation, Leukemic / genetics
Humans
Jurkat Cells
MEF2 Transcription Factors / genetics
Mice
Nitrophenols / pharmacology*
Piperazines / pharmacology
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Prednisolone / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
Sulfonamides / pharmacology*
fms-Like Tyrosine Kinase 3 / genetics
|
| IF |
2.74
|
| Times Cited |
13
|
|
WOS Category
|
MULTIDISCIPLINARY SCIENCES
|
| Resource |
| DNA material |
pMSCVneo-MEF2C (RDB13695) |
